Indocyanine Green Dye Research Articles

Intra-Ureteral Indocyanine Green (ICG) Dye Use During Complex Pelvic Surgery: A Surgical Tutorial and Guide

Intra-Ureteral Indocyanine Green (ICG) Dye Use During Complex Pelvic Surgery: A Surgical Tutorial and Guide

Tumor agnostic ultrasmall nanoprobes for fluorescence-guided surgical resection in peritoneal metastasis.

Surgical excision of metastases is the only curative treatment strategy in peritoneal carcinomatosis management, and the completeness of tumor resection determines the success of the surgery. Tumor-specific fluorescence-guided probes can improve the outcomes of cytoreductive surgery and thereby prognosis. This study aimed to develop and evaluate the feasibility of fluorescently labeled ultrasmall porous silica nanoparticles (UPSN) for image-guided resection of peritoneally disseminated tumors of different origins. Ultrasmall fluorescent nanoprobes were synthesized and characterized for their physicochemical properties and stability. Tumor-specific uptake and biodistribution profiles were evaluated in syngeneic CT26 colorectal and KPC-689 pancreatic cancer murine models. The practicability of real-time optical UPSN-guided resection was examined in the CT26 colorectal cancer model using a surgical stereomicroscope. Quantitative measurements of tumor sensitivity and specificity were performed. Histopathological examination validated in vivo findings about tumor-specific accumulation and safety of ultrasmall fluorescent probes. As-synthesized UPSNs were successfully surface modified with Cy5 or Cy3 dyes maintaining sub-15nm size and near neutral charge which is beneficial for optimized in vivo pharmacokinetics. UPSN-Cy5 demonstrated high tumor-specific uptake and favorable biodistribution profiles in peritoneal metastasis models of CT26 and KPC tumors. Dye-conjugated UPSN enabled resection of microscopic lesions and achieved a higher tumor-to-background ratios in comparison to FDA-approved indocyanine green (ICG) dye in both models. Microscopic evaluation showed tumor localization and off-target safety profile of the UPSN-Cy5. Ultrasmall fluorescent probes were effective in surgical resection of peritoneal metastases with high sensitivity and specificity, thus emerging as promising tumor agnostic agents for image-guided cancer surgery.

P2.14A.07 Learning Curve Analysis of Near-Infrared Fluorescence-Guided Robotic-Assisted Minimally Invasive Esophagectomy with Indocyanine Green Dye

P2.14A.07 Learning Curve Analysis of Near-Infrared Fluorescence-Guided Robotic-Assisted Minimally Invasive Esophagectomy with Indocyanine Green Dye

No more gap-shifting: Stochastic many-body-theory based TDHF for accurate theory of polymethine cyanine dyes.

We introduce an individually fitted screened-exchange interaction for the time-dependent Hartree-Fock (TDHF) method and show that it resolves the missing binding energies in polymethine organic dye molecules compared to time-dependent density functional theory (TDDFT). The interaction kernel, which can be thought of as a dielectric function, is generated by stochastic fitting to the screened-Coulomb interaction of many-body perturbation theory (MBPT), specific to each system. We test our method on the flavylium and indocyanine green dye families with a modifiable length of the polymethine bridge, leading to excitations ranging from visible to short-wave infrared. Our approach validates earlier observations on the importance of inclusion of medium range exchange for the exciton binding energy. Our resulting method, TDHF@vW, also achieves a mean absolute error on a par with MBPT at a computational cost on a par with local-functional TDDFT.

Oxygen Saturation Endoscopic Imaging as a Novel Alternative to Assess Tissue Perfusion During Esophagectomy.

Assessment of gastric conduit perfusion during esophagectomy is crucial to determine its viability and identify the optimal site for anastomosis. Indocyanine green (ICG) fluorescence imaging is commonly used for this purpose, but it is contraindicated in patients with hypersensitivity to ICG, iodine, or shellfish. Oxygen saturation endoscopic imaging (OXEI) is a newer, non-pharmacologic technique for assessing perfusion. We report our experience with OXEI in 3 esophagectomy patients who had contraindications to ICG. All 3 patients underwent robot-assisted esophagectomies. None of the conduits had ischemic areas identified by white light. Using a 5mm laparoscopic specialized camera (ELUXEO Vision, FUJIFILM Healthcare Americas Corp., USA), OXEI was deployed for intracorporeal assessment of gastric conduit perfusion after pull-up into the chest. Postoperative outcomes including anastomotic leaks and complications were recorded. In two patients, OXEI revealed ischemic zones, which were resected to ensure optimal conduit viability. In the remaining patient, OXEI indicated robust vascularity throughout the conduit. All three patients experienced uneventful postoperative courses and were discharged within 10 days. There were no instances of anastomotic leaks or other major complications. In our experience, OXEI is a viable method for intraoperative assessment of gastric conduit perfusion in patients with contraindications to ICG. Prospective studies are needed to validate its efficacy in preventing anastomotic complications and to compare it with other methods of perfusion assessment including gross visual and ICG dye in a larger patient population.

Quantitative evaluation of microenvironmental changes and efficacy of cupping therapy under different pressures based on photoacoustic imaging

Cupping therapy, a traditional Chinese medicinal practice, has been subjected to scientific scrutiny to validate its effects on local tissue microenvironments. This study provides a quantitative assessment of cupping therapy at different negative pressures using photoacoustic imaging. Low-pressure cupping (-20 kPa) significantly improved local blood circulation, evidenced by increased hemoglobin oxygen saturation and vessel dilation that normalized within two hours. In contrast, high-pressure cupping (-30 kPa) led to capillary rupture, bleeding, and tissue edema, similar to the clinical presentation of cupping bruises. Additionally, our research unveiled that −20 kPa cupping expedited the clearance of indocyanine green dye, suggesting enhanced lymphatic drainage, which was further supported by fluorescence imaging. This indicates a potential mechanism for cupping's pain relief effects. Moreover, cupping showed promising results in improving sepsis outcomes in mice, potentially due to its anti-inflammatory properties. This study establishes a foundation for the objective evaluation of cupping therapy, demonstrating that low-pressure cupping is effective in promoting blood and lymphatic flow while minimizing tissue damage, thereby offering a safer therapeutic approach.

Indocyanine green and methylene blue dye guided sentinel lymph node biopsy in patients with penile cancer (PeCa): results of 50 inguinal basins assessed at a single institution in India.

The primary aim of this study was to validate the reliability, sensitivity and safety profile of novel combination of ICG- methylene blue dye as an SN tracer for PeCa. This is a validation and non-randomised prospective observational study involving 25 patients (50 inguinal basins) who underwent SLNB where in ICG and methylene blue were used for localisation. The patients with clinically node negative groins were recruited in the study. SNs were identified intraoperatively using near infrared fluorescence imaging (NIRF Imaging system, SPY-PHI, Stryker, Sweden) and blue dye. The numbers of SNs identified by each tracer and the rates of complications and nodal recurrence during the followup. Overall 137 SNs were identified intraoperatively. Among the 137 SNs excised fluorescence, blue dye and Combined (blue + green) identified 57(41.6%), 27 (19.7%), and 51 (37.2%), respectively. The average number of SLNs removed per patient was 5 (range, 1-11) with sentinel lymph nodes detection rate at 94% (47/50). Seven patients had malignancy on SLNB and underwent ipsilateral radical inguinal lymphadenectomy. One patient had false negative SN and positive node in modified inguinal lymphadenectomy specimen. No adverse events were observed in all cases. The Novel combination of ICG fluorescence-Methylene blue dye technique is simple, reliable and safe. Moreover, it demonstrates a high SLN detection rate with a low false-negative rate, and it avoids radiation exposure.

Electrospun Silk-ICG Composite Fibers and the Application toward Hemorrhage Control.

In trauma and surgery, efficient hemorrhage control is crucial to avert fatal blood loss and increase the likelihood of survival. There is a significant demand for novel biomaterials capable of promptly and effectively managing bleeding. This study aimed to develop flexible biocomposite fibrous scaffolds with an electrospinning technique using silk fibroin (SF) and indocyanine green (ICG). The FDA-approved ICG dye has unique photothermal properties. The water permeability, degradability, and biocompatibility of Bombyx mori cocoon-derived SF make it promising for biomedical applications. While as-spun SF-ICG fibers were dissolvable in water, ethanol vapor treatment (EVT) effectively induced secondary structural changes to promote β-sheet formation. This resulted in significantly improved aqueous stability and mechanical strength of the fibers, thereby increasing their fluid uptake capability. The enhanced SF-ICG interaction effectively prevented ICG leaching from the composite fibers, enabling them to generate heat under NIR irradiation due to ICG's photothermal properties. Our results showed that an SF-ICG 0.4% fibrous matrix can uptake 473% water. When water was replaced by bovine blood, a 25 s NIR irradiation induced complete blood coagulation. However, pure silk did not have the same effect. Additionally, NIR irradiation of the SF-ICG fibers successfully stopped the flow of blood in an in vitro model that mimicked a damaged blood vessel. This novel breakthrough offers a biotextile platform poised to enhance patient outcomes across various medical scenarios, representing a significant milestone in functional biomaterials.

Indocyanine green near infrared fluorescent imaging and its potential role in peripheral nerve repair.

This case series describes the successful use of indocyanine green dye and near infrared fluorescence imaging in primary peripheral nerve repair.

Discovering the potential of biomaterial-based mesoporous and magneto-luminescent nanohybrid (Nd-doped Hydroxyapatite/Fe3O4) for cancer theragnosis

Multimodality nanoplatforms play a crucial role in advancing medical interventions by integrating multiple functionalities into a single system. However, issues like intricate production processes and biocompatibility persist. Herein, a facile synthesis of a biomaterial-based mesoporous nanocarrier, HAp:Nd+SPIONs@mSiO2 is reported. The nanohybrid with ∼100 nm average size, comprised of Nd-doped hydroxyapatite (HAp:Nd) nanophosphor, Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs), and mesoporous silica, exhibiting magneto-luminescent properties. The nanohybrid showed NIR to NIR photoluminescence properties important for deep tissue imaging. The mesoporous nanohybrid was loaded with Indocyanine green (ICG), a photosensitizer and photothermal dye, as a model drug (∼6 μg/mg of nanoparticles) with a high absorption stability retaining >75 % drug until 24 h incubation in pH 6 and 7.4, respectively. Nanoparticles demonstrated dual functionality by generating heat through magnetic and photonic stimulation, as well as producing reactive oxygen species (ROS) upon excitation with 808 nm light. In vitro assays on aggressive triple-negative breast cancer cells (MDA-MB-231) showed the high biocompatibility of nanohybrid with and without ICG, while a significant toxicity was seen after irradiation of NIR light due to ROS production. Noticeably, the nanohybrids also exhibit the ability to monitor temperature changes via Nd3+ associated NIR luminescence. The nanoplatform integrates clinically relevant components like hydroxyapatite, SPIONs, mesoporous silica and ICG, highlighting its potential for translational applications. The developed nanohybrids, with combined NIR-mediated photothermal and photodynamic effects, magnetic photothermal capabilities, and NIR/MR imaging, offer promise in addressing cancer heterogeneity and improving conventional treatments with reduced side effects.

Leveraging Non-Radiative Transitions in Asphaltenes-Derived Carbon Dots for Cancer Photothermal Therapy.

Cancer photothermal therapy leverages the capability of photothermal agents to convert light to heat for cancer cell ablation and necrosis. However, most conventional photothermal agents (Au, CuS, Pd, mesoporous silica nanoparticles, and indocyanine green dye) either face scalability challenges or photobleached upon prolonged irradiation which jeopardizes practical applications. Here, asphaltenes-derived carbon dots (ACDs, 5nm) are rationally engineered as a low-cost and photostable photothermal agent with negligible in vivo cytotoxicity. The abundant water-solvating functional groups on the ACDs surface endows them with excellent water re-dispersibility that outperforms those of most commercial nanomaterials. Photothermal therapeutic property of the ACDs is mechanistically described by non-radiative transitions of excited electrons at 808nm via internal conversions and vibrational relaxations. Consequently, the ACDs offer cancer photothermal therapy in mice within 15 days post-exposure to one-time near infrared irradiation. This pioneering study showcases the first utilization of asphaltenes-based materials for cancer therapy and is expected to arouse further utilization of such materials in various cancer theranostics.

Laparoscopic Sentinel Lymph Node Mapping Using Indocyanine Green Dye in Endometrial Cancer: Experience from a Tertiary Cancer Care Centre in South India

Laparoscopic Sentinel Lymph Node Mapping Using Indocyanine Green Dye in Endometrial Cancer: Experience from a Tertiary Cancer Care Centre in South India

Hypopituitarism, Diabetes Insipidus, and Syndrome of Inappropriate Antidiuretic Hormone Secretion after Pituitary Macroadenoma Surgery with Indocyanine Green Dye.

(1) Background: Pituitary adenomas are benign tumors comprising about 18% of all intracranial tumors, and they often require surgical intervention. Differentiating pituitary tissue from adenoma during surgery is crucial to minimize complications. We hypothesized that using ICG dye would reduce the hormonal complication rates. (2) Methods: A prospective randomized study (February 2019-October 2023) included 34 patients with non-functional macroadenomas of the pituitary gland randomly assigned to receive intraoperative ICG or be in the control group. All underwent endoscopic endonasal transsphenoidal surgery. Pituitary function was assessed preoperatively, immediately postoperatively, and 3-6 months postoperatively. Adenohypophysis function was evaluated with hormonal tests (Cosyntropin stimulation test, TSH, fT3, fT4, prolactin, IGF-1, FSH, LH, and testosterone in men) and neurohypophysis function with fluid balance, plasma and urine osmolality, and serum and urinary sodium. (3) Results: Of the 34 patients (23 men, 11 women; average age 60.9 years), 5.9% in the ICG group developed diabetes insipidus postoperatively, compared to 23.5% in the control group. Adenohypophysis function worsened in 52.9% of the ICG group and in 35.3% of the control group. (4) Conclusions: Our study did not confirm the benefits of using ICG in these surgeries. Further research with a larger sample is needed.

KS‐133/KS‐487 Nanoparticles Exhibit Potent Antitumor Effects through Synergistic LRP1 Targeting and VIPR2 Inhibition: Therapeutic Nanoarchitectonics for Solid Tumors

AbstractVIPR2 is associated with psychiatric disorders, breast cancer metastasis, and cancer immunostimulation. The VIPR2 antagonist KS‐133 changes the polarity of macrophages to the M1 type, and nanoparticles (NPs) releasing KS‐133 exhibit antitumor effects against mouse colon cancer cells (CT26) in vivo. To enhance the antitumor effect of KS‐133 NPs, KS‐133 NPs are combined with the peptide KS‐487 targeting LRP1, which is expressed on CT26 cells. Subcutaneous injection of NPs containing indocyanine green (ICG) fluorescent dye and presenting KS‐487 in CT26 subcutaneous tumor‐bearing mice resulted in significant accumulation of ICG in the CT26 tumor compared to administration of NPs without KS‐487. NPs containing KS‐133 and presenting KS‐487 (KS‐133/KS‐487 NPs) exhibited dose‐dependent antitumor effects in CT26 subcutaneous tumor‐bearing mice; the antitumor effects are more potent than the effects of KS‐133 NPs without KS‐487. In addition, CD8‐positive T cells and macrophages significantly infiltrated into CT26 tumors after injection of KS‐133/KS‐487 NPs. Thus, KS‐133/KS‐487 NPs efficiently deliver KS‐133 to CT26 tumors via LRP1‐targeting and activate immune system cells such as CD8 positive T cells and macrophages via KS‐133 inhibition of VIPR2 signaling, resulting in antitumor effects. These results demonstrate the potential of KS‐133/KS‐487 NPs as a therapeutic candidate for treating solid tumors.

Challenges in flap monitoring with indocyanine green angiography in experimental models

IntroductionNon-invasive angiography with indocyanine green dye facilitates the assessment of flaps. Although ICG angiography has been successfully utilized in clinical settings for human beings, its application in experimental models exhibits certain limitations. This study aimed to address the encountered issues in angiography with different experimental models and introduce a novel modification to the ICG imaging of the McFarlane flap. Materials-methodsRats were randomly divided into three groups: the first group received an epigastric flap (n = 4), the second group received a deep inferior epigastric perforator flap (n = 4), and the third group received a dorsal flap (n = 8). In the first group, sterile silicone background was placed under two flaps. In the second group, no background was used. In the third group, a sterile silicone or aluminum foil was placed under the flaps. Flap perfusions were assessed using fluorescent imaging after flap adaptations, at postoperative 30th minute and 3., 5. and 7. days. Necrosis calculations were performed using all images obtained from the digital camera and the fluorescent imaging. In the third group, the flow velocities were also calculated. All flaps were sent for histopathological examination. ResultsEven with a silicone background, clear perfusion evaluation and determining the threshold value for predicting necrosis rates were challenging. Moreover, a portion of the flaps without background material survived as grafts. Using an aluminum foil background improved image quality by reducing reflection from interior organs. ConclusionThe use of an aluminum foil background is beneficial in non-invasive angiography for assessing flap perfusions accurately and predicting necrosis in experimental animal models.

Use of indocyanine green dye for sentinel lymph node mapping in patients with endometrial cancer and a history of iodinated contrast allergy

ObjectivesSentinel lymph node (SLN) mapping is a surgical technique with high accuracy in detecting metastases while limiting morbidity associated with full lymphadenectomy in endometrial cancer. Cervical injection of indocyanine green (ICG) dye is associated with very high SLN detection rates; however, iodinated contrast allergy has traditionally been viewed as a contraindication to ICG use. The objective of this study was to describe the use of ICG in a population of patients with iodinated contrast allergies undergoing surgical staging for endometrial cancer. MethodsIRB approval was obtained. All patients with clinically early-stage endometrial cancer who underwent minimally invasive surgical staging with SLN mapping with ICG at a single academic institution from 1/1/2017 to 12/31/2020 were identified retrospectively. Patients with reported iodinated contrast allergies prior to surgery were identified. Data were collected through electronic medical record review and compared using descriptive statistics. Results820 patients who underwent minimally invasive surgical staging with SLN mapping with ICG were identified, and 25 had documented iodinated contrast allergies. Documented reactions included rash/hives (n = 10, 40 %), anaphylaxis (n = 6, 24 %), shortness of breath (n = 5, 20 %), diarrhea (n = 1, 4 %), and not specified (n = 3, 12 %). A majority (24/25, 96 %) received 4 mg intravenous dexamethasone during induction of general anesthesia as per the institutional enhanced recovery after surgery (ERAS) protocol. No patients experienced allergic reactions or other adverse events after ICG injection. ConclusionsNo patients in this cohort demonstrated an adverse reaction after ICG injection for SLN mapping. This study supports the reasonable safety of ICG in patients with contrast allergies, particularly when routine ERAS protocols containing dexamethasone are utilized.

Indocyanine green fluorescence perfusion testing in robot-assisted hepatic arterial infusion pump placement

BackgroundHepatic arterial infusion pump (HAIP) treatment is a technique used to treat liver localized malignancy with intra-arterial chemotherapy. Methylene blue is generally administered to verify hepatic perfusion and exclude inadvertent extrahepatic perfusion. The use of indocyanine green dye (ICG) combined with near-infrared (NIR) fluorescence imaging during robot-assisted HAIP placement may be an attractive alternative by providing high contrast without blue discoloration of the operative field.MethodsData was collected retrospectively from 2 centers in the Netherlands. Intraoperative perfusion of the liver segments and extrahepatic perfusion were assessed using ICG/NIR as well as methylene blue on video imaging and correlated to postoperative 99 m-Tc perfusion scintigraphy.Results13 patients underwent robot-assisted surgery for HAIP placement; median length of stay was 4 days, complications occurred in 4 patients. Hepatic perfusion showed identical patterns when ICG was compared with methylene blue. In 1 patient, additional extrahepatic perfusion was found using ICG, leading to further vessel ligation. Intraoperative ICG perfusion was concordant with 99 m-Tc perfusion scintigraphy.DiscussionLiver and extrahepatic perfusion determined by ICG fluorescence imaging is concordant with blue dye perfusion and 99 m-Tc perfusion scintigraphy. Therefore, ICG fluorescence imaging is deemed a safe and reliable technique for perfusion testing during robot-assisted HAIP placement.Graphical abstract

Evaluation of the benefit of indocyanine green as an educational and practical tool for ureteral identification in laparoscopic pelvic surgery: a cross-sectional study

Background Indocyanine green (ICG) is a visible near-infrared fluorescent dye. Several studies have reported its benefit in identifying important anatomical structures, tissue vascularization, and sentinel lymph nodes in the case of tumors. Studies have shown that ICG is critical and safe in gynecologic surgeries. However, research on how ICG dye can help surgeons in laparoscopic surgeries correctly identify the course of the ureter has yet to be further investigated. Method This cross-sectional study enrolled 62 gynecology attending and resident surgeons who were asked to identify the course of the ureter on images of laparoscopic surgeries. The results were then compared with images in which ICG dye highlighted the course of the ureter. The purpose of this study was to detect the ability of surgical assistants and residents to adequately identify the course of the ureter in laparoscopic pelvic surgeries. Results No statistically significant differences were found in terms of year of residency, years of experience, number of laparoscopic procedures attended, and correct identification of ureter course. ICG proved useful in identifying the correct ureteral trajectory. Conclusions ICG can be a valuable tool to improve the correct identification of ureters and improve surgical outcomes.

Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging (FLI)-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy (PTT) research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, two ionic ICG derivatives are transformed into neutral merocyanines (mCy) to achieve much-enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes show similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrate that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics.

Sentinel lymph node detection with indocyanine green and patent blue dye in cervical cancer: A single-centre feasibility study.

Sentinel lymph node (SLN) dissection has been established as standard of care in many tumours. Its use in early cervical cancer is an area of increasing interest and some studies suggest a high detection rate. To explore feasibility of SLN dissection and establish the patient detection rate in women with early cervical cancer. All patients with early cervical cancer, International Federation of Gynaecology and Obstetrics (FIGO) 2018 Stage 1, of any histology who underwent SLN dissection from January 2017 to March 2023 were included. Patients were eligible if they had pelvic confined disease; no suspicious lymph nodes on pre-operative imaging or intra-operatively; tumours <4 cm at the time of surgery and no contra-indications to surgery. Patients were excluded if there was a known allergy to dye or less than six months follow-up data. Sixty-two patients were included in the study and 53% had FIGO stage 1b1 disease. The overall bilateral SLN detection rate was 89%, and the side-specific rate was 94%. Where indocyanine green (ICG) was used alone, the bilateral detection rate was 87% and the side-specific rate was 93%. Where ICG was used with patent blue dye (PTB) the bilateral detection rate was 92% and the side-specific rate was 96%. Where PTB was used alone the bilateral detection rate was 85% and the side-specific rate was 92%. The node positive rate was 6% (7/124) which included isolated tumour cells in four patients. SLN dissection with ICG or PTB is feasible in early-stage cervical cancer.